Water → HCID 58382004, compound

HRID 1628063Notes

Reaction equation

HRID 1628063 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C:13]1[N:30](COCC[Si](C)(C)C)[C:16]2[N:17]=[CH:18][C:19]3[N:20]([C:21]([CH:24]4[CH2:29][CH2:28][CH2:27][O:26][CH2:25]4)=[N:22][CH:23]=3)[C:15]=2[CH:14]=1.C(O)(C(F)(F)F)=O.[NH4+].[OH-].O>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C:13]1[NH:30][C:16]2[N:17]=[CH:18][C:19]3[N:20]([C:21]([CH:24]4[CH2:29][CH2:28][CH2:27][O:26][CH2:25]4)=[N:22][CH:23]=3)[C:15]=2[CH:14]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 14923Ammonium HydroxideHCID 58382088HCID 58382088, compound

Product 1

HCID 58382004HCID 58382004, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 7-(5-methoxy-1-methyl-1H-indol-3-yl)-1-(tetrahydro-2H-pyran-3-yl)-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazine (0.245 g, 0.461 mmol; prepared using J.1 from Preparation #I.1 with tetrahydro-2H-pyran-2-carboxylic acid [Acella], and L.1 with mercury(II) trifluoroacetate) in DCM (5 mL) was added TFA (0.887 mL, 11.5 mmol). After stirring at rt for about 15 h, the mixture was concentrated in vacuo. The material was dissolved in MeOH (5 mL) and then treated with a 30% aqueous NH4OH solution (1.79 mL, 13.8 mmol). The mixture was heated to about 60° C. for about 1 h then cooled to rt. Water was added (10 mL) and the solids were collected by filtration then washed with water (10 mL). The material was dried in a vacuum oven at about 60° C. for about 16 h to provide 7-(5-methoxy-1-methyl-1H-indol-3-yl)-1-(tetrahydro-2H-pyran-3-yl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazine (0.072 g, 39%): LC/MS (Table 2, Method a) Rt=2.16 min; MS m/z 402 (M+H)+. Syk IC50=A.

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. dissolutionThe material was dissolved in MeOH (5 mL)
  3. temperatureThe mixture was heated to about 60° C. for about 1 h
  4. temperaturethen cooled to rt
  5. filtrationthe solids were collected by filtration
  6. washthen washed with water (10 mL)
  7. customThe material was dried in a vacuum oven at about 60° C. for about 16 h

Sources & evidence

ORD record
ord-b024d5be81d043279be7307ab84a8dcd
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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